The aim of this project is to identify structures within muscle that influence regeneration of the neuromuscular junction and to determine the sorts of information they provide. Results to date have revealed that the synaptic portion of the myofiber basal lamina contains factors that direct the formation of active zones in nerve terminals, and the organization of acetylcholine receptors and junctional folds in regenerating myofibers. Moreover at least some of the cues that direct the growth of regenerating axons are provided by the muscle's extracellular matrix. Our objectives for the next year are to 1) examine the characteristics of regenerating myofiber AChRs organized by synaptic basal lamina; 2) determine whether synaptic basal lamina directs the functional differentiation of nerve terminals; 3) determine whether extracellular matrix contains all factors necessary for directing growth of axons to original synaptic sites on myofiber basal lamina; 4) learn whether denervated nerves release a diffusable factor that directs axon growth. For these studies we plan to use a variety of surgical, light and electron microscopical, electrophysiological and biochemical techniques.